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Total synthesis of a functional designer eukaryotic chromosome.

TitleTotal synthesis of a functional designer eukaryotic chromosome.
Publication TypeJournal Article
Year of Publication2014
AuthorsAnnaluru, N, Muller, H, Mitchell, LA, Ramalingam, S, Stracquadanio, G, Richardson, SM, Dymond, JS, Kuang, Z, Scheifele, LZ, Cooper, EM, Cai, Y, Zeller, K, Agmon, N, Han, JS, Hadjithomas, M, Tullman, J, Caravelli, K, Cirelli, K, Guo, Z, London, V, Yeluru, A, Murugan, S, Kandavelou, K, Agier, N, Fischer, G, Yang, K, J Martin, A, Bilgel, M, Bohutski, P, Boulier, KM, Capaldo, BJ, Chang, J, Charoen, K, Choi, WJin, Deng, P, DiCarlo, JE, Doong, J, Dunn, J, Feinberg, JI, Fernandez, C, Floria, CE, Gladowski, D, Hadidi, P, Ishizuka, I, Jabbari, J, Lau, CYL, Lee, PA, Li, S, Lin, D, Linder, ME, Ling, J, Liu, J, Liu, J, London, M, Ma, H, Mao, J, McDade, JE, McMillan, A, Moore, AM, Oh, WChan, Ouyang, Y, Patel, R, Paul, M, Paulsen, LC, Qiu, J, Rhee, A, Rubashkin, MG, Soh, IY, Sotuyo, NE, Srinivas, V, Suarez, A, Wong, A, Wong, R, Xie, WRose, Xu, Y, Yu, AT, Koszul, R, Bader, JS, Boeke, JD, Chandrasegaran, S
JournalScience
Volume344
Issue6179
Pagination55-8
Date Published2014 Apr 4
ISSN1095-9203
KeywordsBase Sequence, Chromosomes, Fungal, DNA, Fungal, Genes, Fungal, Genetic Fitness, Genome, Fungal, Genomic Instability, Introns, Molecular Sequence Data, Mutation, Polymerase Chain Reaction, RNA, Fungal, RNA, Transfer, Saccharomyces cerevisiae, Sequence Analysis, DNA, Sequence Deletion, Synthetic Biology, Transformation, Genetic
Abstract

Rapid advances in DNA synthesis techniques have made it possible to engineer viruses, biochemical pathways and assemble bacterial genomes. Here, we report the synthesis of a functional 272,871-base pair designer eukaryotic chromosome, synIII, which is based on the 316,617-base pair native Saccharomyces cerevisiae chromosome III. Changes to synIII include TAG/TAA stop-codon replacements, deletion of subtelomeric regions, introns, transfer RNAs, transposons, and silent mating loci as well as insertion of loxPsym sites to enable genome scrambling. SynIII is functional in S. cerevisiae. Scrambling of the chromosome in a heterozygous diploid reveals a large increase in a-mater derivatives resulting from loss of the MATα allele on synIII. The complete design and synthesis of synIII establishes S. cerevisiae as the basis for designer eukaryotic genome biology.

DOI10.1126/science.1249252
Alternate JournalScience
PubMed ID24674868
PubMed Central IDPMC4033833
Grant ListGM077291 / GM / NIGMS NIH HHS / United States
R01 GM077291 / GM / NIGMS NIH HHS / United States
R01 GM090192 / GM / NIGMS NIH HHS / United States